Altered DNA methylation is a hallmark of cancer cells, and epigenetic aberrations including gains and losses of DNA methylation also underlie other medical disorders. Such epigenetic aberrations are thought to act in concert with genetic changes, such as chromosome losses and gains, in cancer initiation and progression. In this technology development project we will develop and extensively validate a cost-effective, high-resolution and high-throughput method for simultaneously characterizing genetic aberrations and alterations in DNA methylation genome wide in human cancers. We expect that this method, which we abbreviate MSNP (Methylation-sensitive SNP array analysis), will be useful both for answering fundamental questions such as the relationship between the DNA sequence and its pattern of methylation (genetic/epigenetic interactions and allele-specific DNA methylation) and the relationship between DNA methylation and gene expression, and for achieving important medical objectives including identifying tumor suppressor genes and proto-oncogenes regulated by DNA methylation and finding new and robust markers for cancer diagnosis and detection. Altered DNA methylation is a hallmark of cancer cells, and gains and losses of DNA methylation also underlie other medical disorders. This project is designed to optimize and validate a new method, called MSNP, for detecting and mapping DNA methylation at high resolution across the entire human genome in both normal and cancerous human tissues. Data from MSNP are expected to shed light on cancer pathogenesis and produce new and robust markers for cancer diagnosis and detection. [unreadable] [unreadable] [unreadable]